title: Genistein aglycone effect on bone loss is not enhanced by supplemental calcium and vitamin D3: a dose ranging experimental study.
abstract: Genistein aglycone (GEN) has a favorable effect on bone loss. We investigated the effects of GEN alone or in combination with supplemental calcium and vitamin D(3) in an animal model of bone loss to evaluate if there was additional benefit. Ovariectomized (OVX) and SHAM-OVX rats were used. OVX were divided into 12 groups and randomized to receive: GEN at 27, 54, 200, 500 or 1000 mg (human equivalent dose (HED)/day/ip injection alone or with calcium carbonate (Ca) (360 mg/kg/day/gavages) and vitamin D(3) (D(3)) (50 IU/kg/day/gavages) or Ca/D(3) without GEN or untreated for 6 weeks. SHAM-OVX were randomized into 7 groups and treated with: Ca and D(3) alone or in combination with GEN (same doses as OVX), or left untreated. Bone mineral density (BMD), bone-alkaline phosphatase (b-ALP), collagen C-telopeptides (CTX), osteoprotegerin (OPG) and soluble receptor activator of NFκB ligand (sRANKL) were assessed. Femurs were excised and tested for breaking strength and histology. Uterine weight was analyzed to assess GEN's estrogenic effects on the SHAM-OVX. The most effective dose of GEN, independent of Ca/D(3) supplementation, was 54 mg/day. Higher doses yielded no further improvement in bone biomarkers, histology or strength. Only 1000 mg/day HED of genistein produced statistically significant changes in uterine weight of the SHAM-OVX. This study suggests that 54 mg/day of GEN is the threshold dose for efficacy. In addition, supplemental calcium and vitamin D(3), beyond normal dietary intake do not enhance the effects of genistein on improving measures of bone loss. This observation has implications regarding the use of calcium and vitamin D(3) supplementation.
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bitto
authors.forename: H
authors.initials: H
authors.lastname: Marini
authors.forename: B P
authors.initials: BP
authors.lastname: Burnett
authors.forename: F
authors.initials: F
authors.lastname: Polito
authors.forename: R M
authors.initials: RM
authors.lastname: Levy
authors.forename: N
authors.initials: N
authors.lastname: Irrera
authors.forename: L
authors.initials: L
authors.lastname: Minutoli
authors.forename: E B
authors.initials: EB
authors.lastname: Adamo
authors.forename: F
authors.initials: F
authors.lastname: Squadrito
authors.forename: D
authors.initials: D
authors.lastname: Altavilla
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology; D001851:Bone Diseases, Metabolic / Q000188:drug therapy*; D002119:Calcium Carbonate / Q000494:pharmacology*; D002762:Cholecalciferol / Q000494:pharmacology*; D019245:Compressive Strength; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D005269:Femur / Q000033:anatomy & histology / Q000187:drug effects; D019833:Genistein / Q000008:administration & dosage / Q000627:therapeutic use*; D053244:Osteoprotegerin / Q000187:drug effects; D010052:Ovariectomy; D010936:Plant Extracts / Q000008:administration & dosage / Q000627:therapeutic use; D053245:RANK Ligand / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D029909:Sophora / Q000737:chemistry; D014599:Uterus / Q000187:drug effects
chemical_list: D050071:Bone Density Conservation Agents; D053244:Osteoprotegerin; D010936:Plant Extracts; D053245:RANK Ligand; D002762:Cholecalciferol; D019833:Genistein; D000469:Alkaline Phosphatase; D002119:Calcium Carbonate